Exploring the causal factor effects of hypothyroidism on ischemic stroke: a two-sample Mendelian randomization study.

Background: Observational studies have suggested a possible association between hypothyroidism and increased risk of ischemic stroke. However, a causal relationship remains unclear. Methods: Data on single nucleotide polymorphisms (SNPs) associated with hypothyroidism and ischemic stroke were sourced from the FinnGens database and the UK Biobank of European descent. Both databases underwent separate two-sample Mendelian randomization (MR) analyses. A subsequent meta-analysis of MR results using a random-effects model was conducted to determine the causal relationship between hypothyroidism and ischemic stroke. Results: All five analyses indicated a positive causal relationship between hypothyroidism and ischemic stroke. MR analysis of the association between hypothyroidism and ischemic stroke yielded a result of the inverse variance weighted (IVW) method at 4.7411 (1.3598-16.5308), p = 0.0146. The analysis of ischemic stroke (without excluding controls) yielded a result of the IVW method of 4.5713 (1.3570-15.3986), p = 0.0142. MR analysis with cerebral infarction yielded a result of the IVW method at 1.0110 (1.0006-1.0215), p = 0.0373. The MR analysis with cerebrovascular disease sequelae yielded an IVW method result of 2.4556 (1.0291-5.8595), p = 0.0429. Analysis for the sequelae of cerebrovascular disease (without excluding controls) yielded an IVW method result of 2.4217 (1.0217-5.7402), p = 0.0446. No evidence of heterogeneity or horizontal pleiotropy was found. The meta-analysis of the five MR results was 2.24 (1.18-4.26), p = 0.025. Conclusion: Our two-sample Mendelian randomization study suggested a causal relationship between hypothyroidism and ischemic stroke, indicating that hypothyroidism could be a risk factor for ischemic stroke. However, further studies are required to elucidate the underlying biological mechanisms.

Bibliometric Analysis of Stem Cells in Ischemic Stroke (2001-2022): Trends, Hotspots and Prospects.

Background: Ischemic stroke is a common cerebrovascular accident with a high risk of neurological deficits. Stem cell therapy has progressively attracted the interest of scientists and clinicians due to the benefits of promoting neural regeneration and regulating the microenvironment surrounding the lesion after ischemic stroke. Our study aimed to evaluate the development trends and research hotspots in the field of stem cells and ischemic stroke. Materials and methods: Publications related to stem cells and ischemic stroke were retrieved from the Web of Science from 2001 to 2022. Data analysis and mapping were performed using VOSviewer, Citespace and ImageGP. Results: In total, 1932 papers were included in the analysis. Publications have steadily increased over the past 22 years. China has contributed the maximum number of publications, whereas the USA ranked first in the total number of citations and was considered the center of the international collaboration network. University of South Florida, Henry Ford Hospital, and Oakland University were the most influential institutions. Stroke, Brain Research, and Neural Regeneration Research were the most productive journals. The research in this field was primarily focused on the effects of stem cells on neurogenesis, inflammation, and angiogenesis following ischemic stroke, as well as their therapeutic potential for the disease. In addition, neural stem cells and mesenchymal stem cells are the most commonly utilized stem cells. The topics related to miRNA, extracellular vesicles, exosomes, mesenchymal stem cells, neuroinflammation, and autophagy are current research hotspots. Conclusion: Our bibliometric study provides a novel perspective on the research trends in the field of stem cells and ischemic stroke. The outcome of this study may benefit scientists to identify research hotspots and development directions, thereby advancing the application of stem cell-based therapy for ischemic stroke.

Exploring Research Trend and Hotspots on Oxidative Stress in Ischemic Stroke (2001-2022): Insights from Bibliometric.

Oxidative stress is widely involved in the pathological process of ischemic stroke and ischemia-reperfusion. Several research have demonstrated that eliminating or reducing oxidative stress can alleviate the pathological changes of ischemic stroke. However, current clinical antioxidant treatment did not always perform as expected. This bibliometric research aims to identify research trends, topics, hotspots, and evolution on oxidative stress in the field of ischemic stroke, and to find potentially antioxidant strategies in future clinical treatment. Relevant publications were searched from the Web of Science (WOS) Core Collection databases (2001-2022). VOSviewer was used to visualize and analyze the development trends and hotspots. In the field of oxidative stress and ischemic stroke, the number of publications increased significantly from 2001 to 2022. China and the USA were the leading countries for publication output. The most prolific institutions were Stanford University. Journal of Cerebral Blood Flow and Metabolism and Stroke were the most cited journals. The research topics in this field include inflammation with oxidative stress, mitochondrial damage with oxidative stress, oxidative stress in reperfusion injury, oxidative stress in cognitive impairment and basic research and clinical translation of oxidative stress. Moreover, "NLRP3 inflammasome," "autophagy," "mitophagy," "miRNA," "ferroptosis," and "signaling pathway" are the emerging research hotspots in recent years. At present, multi-target regulation focusing on multi-mechanism crosstalk has progressed across this period, while challenges come from the transformation of basic research to clinical application. New detection technology and new nanomaterials are expected to integrate oxidative stress into the clinical treatment of ischemic stroke better.

Submonolayer biolasers for ultrasensitive biomarker detection.

Biomarker detection is key to identifying health risks. However, designing sensitive and single-use biosensors for early diagnosis remains a major challenge. Here, we report submonolayer lasers on optical fibers as ultrasensitive and disposable biosensors. Telecom optical fibers serve as distributed optical microcavities with high Q-factor, great repeatability, and ultralow cost, which enables whispering-gallery laser emission to detect biomarkers. It is found that the sensing performance strongly depends on the number of gain molecules. The submonolayer lasers obtained a six-order-of-magnitude improvement in the lower limit of detection (LOD) when compared to saturated monolayer lasers. We further achieve an ultrasensitive immunoassay for a Parkinson's disease biomarker, alpha-synuclein (α-syn), with a lower LOD of 0.32 pM in serum, which is three orders of magnitude lower than the α-syn concentration in the serum of Parkinson's disease patients. Our demonstration of submonolayer biolaser offers great potentials in high-throughput clinical diagnosis with ultimate sensitivity.

Silicon composition and stoichiometric ratios with other nutrients in the lower Minjiang River, Southeast China.

Over the past decades, rivers have delivered imbalanced nutrient loads to coastal marine ecosystems due to human activities, which leads to serious regional or global eutrophication problems. The Minjiang River is heavily influenced by human activities. To understand the changing characteristics of nutrient transport ratios in the Minjiang River waters, we measured the seasonal variations of carbon, nitrogen, phosphorus and silicon nutrients in the lower surface waters of the Minjiang River between July 2019 and July 2020. The results showed that the annual average contents of dissolved silicon (DSi), lithogenic silicon (LSi) and biogenic silicon (BSi) in the surface waters of the lower Minjiang River were 5.30, 4.58 and 2.37 mg·L-1, respectively. There were large seasonal differences among these parameters, with higher content of DSi than LSi and BSi in summer, higher content of DSi than BSi and LSi in autumn and higher content of LSi than DSi and BSi in winter. The proportions of DSi in total silicon tended to decrease gradually from land to sea, while the proportion of BSi was on the contrary. In term of stoichiometric ratios, the Minjiang River mostly presented carbon or phosphorus limitation and was unlimited by silicon or nitrogen. About 1.03×1010 mol DSi and 0.46 ×1010 mol BSi were delivered via the Minjiang River to the ocean yearly, showing a decreasing trend year by year. Based on the data in recent years, the nutrient loads of carbon, nitrogen, and phosphorus transported by Minjiang River showed an increasing trend. The imbalanced nutrient loads may lead to changes in the structure and function of the river, estuary, and offshore ecosystems. The study of nutrient stoichiometric ratios can provide a theoretical basis for solving the problems in structural balance of nutrients and eutrophication in Minjiang River estuary and adjacent marine waters.

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning.

BACKGROUND: Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children. It is associated with high rates of morbidity and mortality, and rapid detection and administration of antimicrobials have been emphasized. The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness. METHODS: Three gene expression datasets were available from the Gene Expression Omnibus collection. First, the differentially expressed genes (DEGs) were found with the use of the R program, and then gene set enrichment analysis was carried out. Subsequently, the DEGs were combined with the major module genes chosen using the weighted gene co-expression network. The hub genes were identified by the use of three machine-learning algorithms: random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator. The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes. In addition, the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). The relationship between the diagnostic markers and infiltrating immune cells was further studied. RESULTS: Overall, after overlapping key module genes and DEGs, we detected 402 overlapping genes. As pediatric sepsis diagnostic indicators, CYSTM1 (AUC = 0.988), MMP8 (AUC = 0.973), and CD177 (AUC = 0.986) were investigated and demonstrated statistically significant differences (P < 0.05) and diagnostic efficacy in the validation set. As indicated by the immune cell infiltration analysis, multiple immune cells may be involved in the development of pediatric sepsis. Additionally, all diagnostic characteristics may correlate with immune cells to varying degrees. CONCLUSIONS: The candidate hub genes (CD177, CYSTM1, and MMP8) were identified, and the nomogram was constructed for pediatric sepsis diagnosis. Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.

Phase-Transition Microcavity Laser.

Liquid-crystal microcavity lasers have attracted considerable attention because of their extraordinary tunability and sensitive response to external stimuli, and because they operate generally within a specific phase. Here, we demonstrate a liquid-crystal microcavity laser operated in the phase transition in which the reorientation of liquid-crystal molecules occurs from aligned to disordered states. A significant wavelength shift of the microlaser is observed, resulting from the dramatic changes in the refractive index of liquid-crystal microdroplets during the phase transition. This phase-transition microcavity laser is then exploited for sensitive thermal sensing, enabling a two-order-of-magnitude enhancement in sensitivity compared with the nematic-phase microlaser operated far from the transition point. Experimentally, we demonstrate an exceptional sensitivity of -40 nm/K and an ultrahigh resolution of 320 µK. The phase-transition microcavity laser features compactness, softness, and tunability, showing great potential for high-performance sensors, optical modulators, and soft matter photonics.

Occurrence and Molecular Variability of the Main Kiwifruit Viruses in the Sichuan Province of China.

Viruses cause important yield losses in kiwifruit. Here, we studied the occurrence and population structure of the major kiwifruit viruses in the Sichuan province of China. RT-PCR results showed the presence of Actinidia virus A (AcVA), Actinidia virus B (AcVB), Actinidia chlorotic ringspot-associated virus (AcCRaV), and the cucumber mosaic virus (CMV). AcCRaV was widely distributed, followed by CMV. These two viruses were often detected in co-infection with AcVA and AcVB. The virus detection rate was positively correlated with vine age. Four phylogenetic groups of AcVA and AcVB were identified, with AcVA isolates clustering mainly in subgroup I, and AcVB isolates clustering mainly in subgroups II, III, and IV. All CMV isolates clustered in subgroup II, and AcCRaV isolates clustered in subgroup IA. The genome of AcVA and AcCRaV was under negative selection pressure, while the genome of AcVB and CMV was under positive selection pressure. All the viruses, except AcVB, were in a state of expansion. The full-length genome of the most widely distributed AcCRaV isolate in kiwifruits in the Sichuan province was characterized by sequencing. Unique eight-nucleotide (TTTTTGAT) repeats were found in the 5'-terminal non-coding region of the AcCRaV RNA3 in a possible association with reduced disease symptoms. This is the first study of kiwifruit viruses in Sichuan.

Exopolysaccharides from Lactobacillus plantarum reduces cadmium uptake and mitigates cadmium toxicity in rice seedlings.

Exopolysaccharides (EPSs) can be used as effective exogenous substances to alleviate the toxic effect of cadmium (Cd) on rice and other crops, thus improving plant growth characteristics under stress conditions, and reducing the accumulation of Cd in grains, but the underlying mechanism is still unclear. In the present work, the effects of EPSs from Lactobacillus plantarum on the efficiency of Cd absorption and distribution in rice seedlings under Cd stress were investigated. The results revealed that growth of rice seedlings was severely inhibited by exposure to Cd, resulting in the decrease of plant height, leaf length and biomass. This inhibition phenomenon was alleviated by the addition of EPSs from L. plantarum LPC-1. The underlying mechanism might be that EPSs could facilitate the accumulation efficiency of Cd in rice roots and reduce the transportation rate of Cd from root to leaves, therefore decreasing the Cd content in leaves. Further research showed that Cd contents in the cell wall fraction of the rice seedling root were increased by the addition of EPSs, while the proportions of Cd in the cell organelle and cell soluble component were reduced. Application of EPSs promotes the proportion of pectate- and protein- integrated Cd in rice roots. While the content of water-soluble Cd, which is more toxic to plants, decreased continuously both in roots and leaves. Our study clearly confirmed the positive effects of EPSs on alleviating Cd toxicity and decreasing Cd translocation in rice above-ground parts. Furthermore, the subcellular distribution and chemical forms of Cd in different rice seedlings parts were also affected by the addition of EPSs, which might be an important potential mechanism for EPSs in respect of alleviating Cd toxicity for rice. These findings provided a foundation for the application of exogenous substances on improving the growth performance of crops under heavy metal stress.

LncRNA KCNQ1OT1 promotes the metastasis of ovarian cancer by increasing the methylation of EIF2B5 promoter.

BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as regulators of human malignancies, including ovarian cancer (OC). LncRNA KCNQ1OT1 could promote OC progression, and EIF2B5 was associated with development of several tumors. This project was aimed to explore the role of lncRNA KCNQ1OT1 in OC development, as well as the involving action mechanism. METHODS: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) or Western blotting was employed to determine the expression levels of KCNQ1OT1 and EIF2B5. OC cell proliferation was evaluated by MTT and colony formation assays, and wound healing and Transwell assays were implemented to monitor cell migration and invasion, respectively. The methylation status of EIF2B5 promoter was examined by MS-PCR, to clarify whether the expression of EIF2B5 was decreased. The binding activity of KCNQ1OT1 to methyltransferases DNMT1, DNMT3A and DNMT3B was determined by dual luciferase reporter assay or RIP assay, to explore the potential of KCNQ1OT1 alters the expression of its downstream gene. ChIP assay was carried out to verify the combination between EIF2B5 promoter and above three methyltransferases. RESULTS: Expression of lncRNA KCNQ1OT1 was increased in OC tissues and cells. EIF2B5 expression was downregulated in OC, which was inversely correlated with KCNQ1OT1. Knockdown of KCNQ1OT1 inhibited OC cell proliferation and metastasis. KCNQ1OT1 could downregulate EIF2B5 expression by recruiting DNA methyltransferases into EIF2B5 promoter. Furthermore, interference of EIF2B5 expression rescued KCNQ1OT1 depletion-induced inhibitory impact on OC cell proliferation and metastasis. CONCLUSION: Our findings evidenced that lncRNA KCNQ1OT1 aggravated ovarian cancer metastasis by decreasing EIF2B5 expression level, and provided a novel therapeutic strategy for OC.

Dissipative Acousto-optic Interactions in Optical Microcavities.

We propose and demonstrate experimentally the strong dissipative acousto-optic interaction between a suspended vibrating microfiber and a whispering-gallery microcavity. On the one hand, the dissipative response driven by an external stimulus of acoustic waves is found to be stronger than the dispersive response by 2 orders of magnitude. On the other hand, dead points emerge with the zero dissipative response at certain parameters, promising the potentials in physical sensing such as precise measurements of magnetic field and temperature. The strong dissipative acousto-optic interaction is then explored for ultrasensitive detection of broadband acoustic waves. A noise equivalent pressure as low as 0.81 Pa at 140 kHz in air is demonstrated experimentally, insensitive to cavity Q factors and does not rely on mechanical resonances.

Biopsychosocial risk factors of depression during menopause transition in southeast China.

OBJECTIVE: More than 2 billion women are experiencing menopause transition in China and some of them suffered from depression; while the risk factors of depression during menopause transition were still unclearin China. We aimed to investigate the risk factors in mid-life women in Southeast China. METHOD: This study included 1748 Chinese women aged 40-65 years-old who visited gynecology outpatient department of Women's hospital School of Medicine, Zhejiang University during 2010-2018. Demographic information was collected, and the modified Kupperman Menopausal Index (mKMI) and Hamilton Rating Scale for Depression were assessed. Circulating levels of sex hormones were tested. Ordinal logistic regression analysis was performed to identify risk factors for depression. RESULTS: The prevalence of depression symptoms was 47.43%. The majority of women had mild (38.56%) or moderate depressive symptoms (8.00%); only 0.86% had severe depressive symptoms. Compared with perimenopausal women, postmenopausal women had increased risks of more severe depression. The associations between menopausal syndromes and the intensity of depression were strongly positive (OR 6.69, 95% CI 5.39-8.29). Elder age, higher follicle stimulating hormone levels, lower estradiol levels, and fewer parity were positively related with the intensity of depression. Among postmenopausal women, underweight, mKMI > 14, earlier age at menopause, shorter reproductive period, and longer duration after menopause were risk factors for incresed intensity of depression. CONCLUSIONS: The results demonstrated a high proportion of depression in women complaining of menopause. Menopausal symptoms were strongly related to the intensity of depression. In postmenopausal women, estrogen related events are associated with the intensity of depression. Gynecological endocrinologists in China should consider screening for depression in high-risk women.

CircAHNAK upregulates EIF2B5 expression to inhibit the progression of ovarian cancer by modulating the JAK2/STAT3 signaling pathway.

Recent studies highlighted non-coding RNAs as potential therapeutic targets in ovarian cancer. We aimed to investigate the roles of circAHNAK in ovarian cancer pathogenesis. Here, RNA immunoprecipitation, dual-luciferase reporter assay and RNA fluorescence in situ hybridization were adopted to determine circAHNAK, miR-28 or EIF2B5 interaction. CCK-8 assay was used to detect cell proliferation. Wound healing and Transwell assays were employed to assess cell migration and invasion, respectively. Flow cytometry was performed to measure cell apoptosis. The roles of circAHNAK on tumor growth in vivo were evaluated using subcutaneous xenograft model. The expression levels of circAHNAK, miR-28, EIF2B5, markers of EMT and JAK2/STAT3 pathway were measured by qRT-PCR, western blotting or immunohistochemistry staining. We reported that circAHNAK was decreased in ovarian cancer tissues. Forced expression of circAHNAK promoted apoptosis and inhibited cell proliferation, migration, invasion, EMT and JAK2/STAT3 signaling pathway. Mechanistically, circAHNAK acted as a miR-28 sponge. CircAHNAK deficiency resulted in the amassing of miR-28, which was elevated in ovarian cancer and promoted cancer cell malignancy. MiR-28 in turn inhibited EIF2B5 expression. Silence of EIF2B5 abolished the anticancer effects of miR-28 inhibitor. CircAHNAK overexpression retarded tumor growth in vivo, along with the decreased miR-28 and increased EIF2B, as well as EMT inhibition. In conclusion, circAHNAK targets miR-28 to upregulate EIF2B5 expression, thus inhibits progression of ovarian cancer by suppressing JAK2/STAT3 signaling pathway.

Single-molecule optofluidic microsensor with interface whispering gallery modes.

Label-free sensors are highly desirable for biological analysis and early-stage disease diagnosis. Optical evanescent sensors have shown extraordinary ability in label-free detection, but their potentials have not been fully exploited because of the weak evanescent field tails at the sensing surfaces. Here, we report an ultrasensitive optofluidic biosensor with interface whispering gallery modes in a microbubble cavity. The interface modes feature both the peak of electromagnetic-field intensity at the sensing surface and high-Q factors even in a small-sized cavity, enabling a detection limit as low as 0.3 pg/cm2 The sample consumption can be pushed down to 10 pL due to the intrinsically integrated microfluidic channel. Furthermore, detection of single DNA with 8 kDa molecular weight is realized by the plasmonic-enhanced interface mode.

Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Approximately 80% of patients initially diagnosed with locally advanced or metastatic disease survive only 4-11 months after diagnosis. Tremendous efforts have been made toward understanding the biology of PDAC. RESULTS: In this study, we first utilized next-generation sequencing technique and existing microarray datasets to identify significant differentially expressed genes between PDAC and non-tumor adjacent tissue. By comparing top significant survival genes in PDAC Gene Expression Profiling Interactive Analysis database and PDAC transcriptome data from patients, our integrated analysis discovered five potential central genes (i.e., MYEOV, KCNN4, FAM83A, S100A16, and DDX60L). Subsequently, we analyzed the cellular functions of the potential novel oncogenes MYEOV and DDX60L, which are highly expressed in PDAC cells. Notably, the knockdown of MYEOV and DDX60L significantly inhibited the metastasis of cancer cells and induced apoptosis. Further RNA sequencing analyses showed that massive signaling pathways, particularly the TNF signaling pathway and nuclear factor-kappa B (NF-κB) signaling pathway, were affected in siRNA-treated cancer cells. The siDDX60L and siMYEOV significantly inhibited the expression of chemokine CXCL2, which may potentially affect the tumor microenvironment in PDAC tissues. CONCLUSIONS: The present findings identified the novel oncogene DDX60L, which was highly expressed in PDAC. Transcriptome profiling through siRNA knockdown of DDX60L uncovered its functional roles in the PDAC in humans.

Morvan syndrome associated with LGI1 antibody: a case report.

BACKGROUND: Morvan syndrome (MoS) is a rare autoimmune syndrome associated with antibodies against two kinds of potassium channel proteins, contactin associated protein-like 2 (CASPR2) and leucine-rich glioma inactivated protein 1 (LGI1). MoS patients with only LGI1-antibody seropositivity have rarely been reported. Here, we describe a 64-year-old male MoS patient with only LGI1-antibody seropositivity. CASE PRESENTATION: A 64-year-old male patient was referred to our hospital due to limb pain, widespread myokymia, insomnia, constipation, and hyperhidrosis for 1 month. The patient was diagnosed with MoS based on the clinical symptoms and positive LGI1-antibody in serum. He was treated with intravenous immunoglobulin (IVIG), intravenous methylprednisolone followed by oral prednisone, and other drugs for symptomatic relief. Several days later, myokymia and insomnia symptoms improved. After 60 days of follow-up, all the drugs had been stopped for 2 weeks, and the patient achieved complete remission without any medical side effects. CONCLUSION: We report the clinical characteristics of a Chinese MoS patient with only LGI1-antibody seropositivity, and further support the view that non-neoplasm MoS patients respond well to immunotherapy.

1/f-noise-free optical sensing with an integrated heterodyne interferometer.

Optical evanescent sensors can non-invasively detect unlabeled nanoscale objects in real time with unprecedented sensitivity, enabling a variety of advances in fundamental physics and biological applications. However, the intrinsic low-frequency noise therein with an approximately 1/f-shaped spectral density imposes an ultimate detection limit for monitoring many paramount processes, such as antigen-antibody reactions, cell motions and DNA hybridizations. Here, we propose and demonstrate a 1/f-noise-free optical sensor through an up-converted detection system. Experimentally, in a CMOS-compatible heterodyne interferometer, the sampling noise amplitude is suppressed by two orders of magnitude. It pushes the label-free single-nanoparticle detection limit down to the attogram level without exploiting cavity resonances, plasmonic effects, or surface charges on the analytes. Single polystyrene nanobeads and HIV-1 virus-like particles are detected as a proof-of-concept demonstration for airborne biosensing. Based on integrated waveguide arrays, our devices hold great potentials for multiplexed and rapid sensing of diverse viruses or molecules.

Polymorphism of FGD4 and myelosuppression in patients with esophageal squamous cell carcinoma.

Background: Chemotherapy-related adverse events may restrain taxane/cisplatin administration as a regimen for patients with esophageal squamous cell carcinoma. Genetic polymorphisms may contribute to adverse event susceptibility. Method & results: The authors genotyped ten SNPs from five genes (rs1045642, rs2032582 and rs3213619 of ABCB1; rs2231137 and rs2231142 of ABCG2; rs246221 of ABCC1; rs3740066 of ABCC2; and rs10771973, rs12296975 and rs1239829 of FGD4) in 219 patients with esophageal squamous cell carcinoma treated with taxane/cisplatin. Patients with severe toxicities were compared with those with minor or no adverse events by unconditional logistic regression models and semi-Bayesian shrinkage. After adjustment for age and sex, with the null prior, FGD4 rs1239829 was statistically significantly related to grade 3-4 leukopenia (odds ratio [95% CI] in dominant model = 1.77 [1.04-3.03]). Conclusion: The minor allele of FGD4 rs1239829 was related to grade 3-4 leukopenia in patients with esophageal squamous cell carcinoma treated with taxane/cisplatin, with unclear biological mechanism.

Lay abstract Taxane/cisplatin is the main chemotherapy regimen in patients with esophageal squamous cell carcinoma in China. Many patients suffer from neurotoxicity or bone marrow suppression, such as decreased white blood cells. Higher-grade adverse events, in particular, usually result in chemotherapy dose reduction or treatment termination. Researchers explored the associations between genetics and chemotherapy toxicity and found that the genetic variant (SNP rs1239829) of the gene FGD4 was related to serious white blood cell decline in patients with esophageal squamous cell carcinoma who were treated with the taxane/cisplatin regimen.

Laser particles with omnidirectional emission for cell tracking.

The ability to track individual cells in space over time is crucial to analyzing heterogeneous cell populations. Recently, microlaser particles have emerged as unique optical probes for massively multiplexed single-cell tagging. However, the microlaser far-field emission is inherently direction-dependent, which causes strong intensity fluctuations when the orientation of the particle varies randomly inside cells. Here, we demonstrate a general solution based on the incorporation of nanoscale light scatterers into microlasers. Two schemes are developed by introducing either boundary defects or a scattering layer into microdisk lasers. The resulting laser output is omnidirectional, with the minimum-to-maximum ratio of the angle-dependent intensity improving from 0.007 (-24 dB) to > 0.23 (-6 dB). After transfer into live cells in vitro, the omnidirectional laser particles within moving cells could be tracked continuously with high signal-to-noise ratios for 2 h, while conventional microlasers exhibited frequent signal loss causing tracking failure.